Replenish, Replace and Rejuvenate, the Three Rs That Will Alter Human Existence

Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers can regrow entire bodies. Sharks replace lost teeth, as many as 20,000 throughout a lifespan. So why can’t we do the same?

The answer: Through cutting-edge innovations in regenerative medicine, research is underway to do just that. In 2019, investors pumped $10 billion into this field, and currently, there are over 1,000 clinical trials underway trying regenerative treatments on 60,000 patients.

As Big Data and Artificial Intelligence (AI) transform medicine, regenerative medicine will take us to these three Rs:

1. Replenish: Stem Cells – the Regenerative Engine of the Body
2. Replace: Organ Regeneration and Bioprinting
3. Rejuvenate: Young Blood & Parabiosis

1. Replenish

Stem cells are undifferentiated cells that transform into specialized cells from embryos to when we are born and beyond. They can be found in many areas of the body. Stem cells differentiate to become heart, neurons, liver, lung, skin and other specialized tissues. They also can divide and produce more stem cells.

As a child or young adult, we have stem cells in large supply. They trigger when the body needs to repair itself. They are summoned to sites where there is damage or inflammation.

As we age, the supply of stem cells diminishes by as much as 100- to 10,000-fold throughout different tissues and organs. Stem cells also undergo genetic mutations over a lifespan which reduces their quality and effectiveness at repairing damage.

If you could restore and rejuvenate a body’s stem cell population we can extend our healthy years dramatically. One way to do this would be to extract and concentrate our autologous adult stem cells harvested from adipose (fat) tissue or bone marrow. Another source comes from umbilical cords and placentas kept after birth.

The advantage of the latter over the former is these stem cells have not been subject to aging like those found in adult adipose tissue or bone marrow. Umbilical and placenta stem cells provide the undamaged software of a newborn and when cultured to multiply, can be injected into joints or administered intravenously as a rejuvenation therapy. Using these stem cells can help to fight inflammation, autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.

A burgeoning field, stem cell research has seen a 40-fold increase in scientific publications over the last few years. The market globally is estimated to grow to $14.8 billion USD by 2022, growing at an annual growth rate of 14.7%.

Examples of regenerative treatments include:

• Kohji Nishida at Osaka University in Japan who is discovering a new way to nurture and grow the tissues that make up the human eye. They are growing retinas, corneas, lenses, and more using only a small sample of adult skin.
• A Stanford University study has used stem cell treatments to improve the motor function of seven of eighteen stroke victims. The treatment has potential for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s and ALS.
• Doctors from the USC Neurorestoration Center and Keck Medicine at USC have injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. After three months the patient showed dramatic improvement in sensation and movement of both arms.
• In 2019, doctors in the United Kingdom cured a patient with HIV for the second time using stem cells. After giving a cancer patient (who also had HIV) an allogeneic hematopoietic stem cell treatment for Hodgkin’s Lymphoma, the patient went into long-term HIV remission, 18 months and counting at the time of the study’s publication.

2. Replace

Every 10 minutes an American is added to an organ transplant waiting list. As of March 2020, 112,000 people were waiting for replacement organs. Countless more people never make it to the waitlist with an average of 20 dying each day. The result, 35% or approximately 900,000 people can be prevented from dying with better and more timely access to replacement organs. Promising a remedy to organ shortages, replacement and regenerative medicine represents a massive opportunity.

The opportunity has led to emerging organ entrepreneurs. One of these is United Therapeutics, started by Dr. Martine Rothblatt, a one-time aerospace entrepreneur and founder of Sirius Satellite Radio.

Personal circumstances led to a change of careers when Rothblatt’s daughter developed a rare lung disease. Her “Moonshot” project to replace her daughter’s unhealthy lungs, and others with similar affliction, has become a major business opportunity pursuing three disruptive strategies that could change medical transplants forever.

Rothblatt’s company is United Therapeutics where she is CEO. With an initial focus on diseases of the lung, she has set out to create replacement lungs. To accomplish this goal, she has pursued a number of technologies in parallel including.

A. 3D Printed Organs

In 2017 she teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter. She teamed up with another company, 3Scan, to create maps of the lungs structures and interior using detailed micro slices programmed into a bioprinter.

An ultraviolet laser passing light through a shallow pool of collagen doped with photosensitive molecules served as the medium for the build. The laser targeted the areas identified by the mapping causing collagen to cure and form a scaffold to which human cells attach. So far the technology has been able to produce lung structures with resolutions of 20 micrometers. The end goal is to get to one micrometer to achieve a functioning replacement for a human lung. Once a scaffold capable of these dimensions can be built it will be infused with living stem cells using recellularization. Stem cells will grow and differentiate, populating the scaffolding, and producing a functional lung.

Can it be done? In 2018, Harald Ott, an experimental surgeon at Harvard University reported that he had pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ displayed rudimentary lung function.

B. Xenotransplantation

Rothblatt is pursuing the transplanting of animal organs into humans which is known as xenotransplantation. Because an adult pig has organs similar in size and shape to those of humans, her company is focusing on genetically engineering pigs to harvest their organs for human transplants. “It’s actually not rocket science,” said Rothblatt in a 2015 TED talk. “It’s editing one gene after another.”

To accomplish this goal, her company has made investments in Revivicor Inc. and Synthetic Genomics Inc. signing funding agreements with the Universities of Maryland, and Alabama, and New York-Presbyterian/Columbia University Medical Center to start a xenotransplantation program for hearts, kidneys and lungs. Rothblatt hopes to see the final results in three to four years. The end goal for the company will be to produce up to 1,000 sets of healthy pig lungs, called xenolungs, annually from genetically engineered pigs.

C. Ex Vivo Perfusion

Today only 30% of human-donated lungs meet transplant criteria. Of these, 85% remain usable upon arrival at a surgical site for implantation. The end result, nearly 75% of donated lung tissues never get used by recipients in need of a transplant.

But what if the donated lung tissue could be rejuvenated?

In 2016, Rothblatt invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that has developed the XVIVO Perfusion System which takes marginal-quality lungs initially fail to meet transplantation standard-of-care criteria and perfuses and ventilates them in normothermic conditions, to provide an opportunity for surgeons to reassess their transplant suitability. The perfusion system can also be used with heart, kidney, and liver tissue for transplantation.

Rejuvenate

Researchers at Stanford and Harvard University have demonstrated that older animals when transfused with blood from young ones experience regeneration in many of their tissues and organs. The opposite is true as well that when young animals are transfused with blood from older donors, they experience accelerated aging.

Elevian (a Harvard University spinoff) is using this “young blood” effect in its approach to studying longevity. CEO Mark Allen, MD, is among the founders along with a dozen MDs and PhDs from the university. They have identified specific factors responsible for the effect described in the previous paragraph.

A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, which, when injected into older mice, reproduces regenerative effects in the heart, brain, muscles, lungs, and kidneys. Further, GDF11 reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, boosts exercise capacity, increases brain function and cerebral blood flow, and even improves metabolism.

From this Elevian is developing a number of therapeutics to regulate GDF11 and other circulating factors with a goal to restore the body’s natural regenerative capacity. The company believes with its current research it can counter the root causes of age-associated disease promising to reverse or prevent many of them and to extend a healthy lifespan.

Final Thoughts

In 1992, the futurist Leland Kaiser created the term regenerative medicine. He called it “A new branch of medicine…that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.” From these initial roots has grown an industry that in 2018 generated $23.8 billion USD and is projected to exceed $151 billion by 2026.

If the work described here pans out, the road ahead for improvements to human health will be enormous. Imagine having the ability to regenerate, replenish, and replace entire organs and metabolic systems on command.

Are there unintended consequences to Peter’s hopeful description of the biomedical breakthroughs that lie ahead? Extending the natural lifespan and making for a longer and healthier lives in a person’s 70s, 80s, 90s, and even 100s and beyond comes with an added burden to the planet which already has 7.8 billion people on it. What are the implications for work and retirement? What are the implications for subsequent generations seeking the jobs of those who are older and no longer prepared to retire because of aging and disease? 

At the beginning of the 20th century, the average human lifespan was 40. By the beginning of the 21st century, it had almost doubled. By 2100, will it double again? Peter Diamandis is convinced it will and we are seeing in this article the beginnings of the technologies that will make that a reality.